The use of solid phase synthesis techniques for the synthesis of polypeptides and oligonucleotides is well known in the art. More recently, the use of solid phase techniques for the synthesis of small organic molecules has become a major focus of research. Of prime importance has been the ability of solid phase techniques to be automated, with an attendant increase in compound throughput and efficiency in research. This has been exploited with great vigor in the area of pharmaceutical research where it has been estimated that 10,000 compounds must be synthesized and tested in order to find one new drug (Science, 259, 1564, 1993). The focus on combinatorial chemistry techniques to increase compound throughput has now become almost universal in the pharmaceutical and agricultural industries.
An additional aspect relates to the chemical diversity of the compound stocks that are available for screening in pharmaceutical companies in the search for new lead structures. These have tended to be limited to the classes of compounds previously investigated through medicinal chemical techniques within each company. Therefore the availability of new classes of molecules for screening has become a major need.
The movement of a chemical reaction from a single reaction in a flask to an experiment producing hundreds or thousands of molecules of varied structure simultaneously in a robot in not a simple process. Consequently, although many classes of organic reactions have now been shown to work on solid phase, a great deal of research is required in order to optimize each new reaction that a chemist wants to undergo this conversion. This optimization phase has become the major stumbling block and the major time-consuming element in modern solid phase combinatorial chemistry research.
In view of the above, the field of pharmaceutical and agricultural research has a strong need for highly flexible routes to novel classes of compounds for screening and clinical testing. The principle object of this patent is to provide an exceptionally flexible process for the high throughput production of many classes of organic molecules. Some of the chemical ring systems attainable through this technology are completely novel and some of the ring systems have value as known, pharmacologically useful agents.